Phosphatidylinositol 3-kinase (PI3K) is known as a kind of phosphorylases of phosphatidylinositol that phosphorylates 3-position of an inositol ring, and is expressed over a wide range throughout the body. The PI3K is known to be activated by stimulation including growth factors, hormones and the like, activate Akt and PDK1, and be involved in survival signals that inhibit cell death, cytoskeleton, glucose metabolism, vesicular transport and the like. In addition, the phosphatidylinositols phosphorylated at position 3 that are formed by PI3K function as messengers of these information transfer systems (Phosphatidylinositol 3-kinases in tumor progression. Eur. J. Biochem. 268, 487-498 (2001); Phosphoinositide 3-kinase: the key switch mechanism in insulin signaling. Biochem. J. 333, 471-490 (1998); Distinct roles of class I and class III phosphatidylinositol 3-kinase in phagosome formation and maturation. J. C. B., 155(1), 19-25 (2001) and the like).
PI3K is categorized into three classes consisting of Class I, Class II and Class III according to the type of phosphatidylinositols serving as a substrate.
Although Class 1 enzymes form phosphatidylinositol (3,4,5)-triphosphate [PI(3,4,5)P3] by using phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] as a substrate in vivo, it is able to use phosphatidylinositol (PI) and phosphatidylinositol (4)-phosphate [PI(4)P] as a substrates in vitro. Further, Class I enzymes are categorized into Class Ia and Ib according to the activation mechanism. Class Ia includes the p110α, p110β and p110δ subtypes, and each forms a heterodimer complex with a regulatory subunit (p85) and is activated by a tyrosine kinase receptor and the like. Class 1b includes a p110γ subtype that is activated by the βγ subunit (Gβγ) of a trimer G protein, and forms a heterodimer with a regulatory subunit (p110).
Class II enzymes include the PI3KC2α, C2β and C2γ subtypes, that use PI and PI(4)P as substrates. These enzymes have a C2 domain on the C terminal, and regulatory subunits as observed for Class I enzymes have not yet to be discovered.
Class III enzymes only use PI as a substrate, and are reported to be involved in membrane transport control as a result of interaction between p150 and human Vps34, a human homolog of Vps34 isolated from yeast.
As a result of analyses using these PI3K knockout mice, p110δ in Class Ia has been reported to be involved in the differentiation and function of T cells and B cells, while p110γ in Class 1b has been reported to be involved in abnormalities of migration of eosinophils, mast cells, platelets and myocardial cells (Phosphoinositide 3-kinase signaling—which way to target? Trends in Pharmacological Science, 24(7), 366-376 (2003)).
On the basis of these results, the targeting of p110δ and p110γ of Class I is expected to be useful against autoimmune diseases, inflammations, asthma, heart disease and the like.
Recently, a gene amplification of PIK3CA encoding p110α, constitutive activation due to mutation, and high expression of p110α at the protein level have been reported in numerous types of cancers (and particularly ovarian cancer, colon cancer and breast cancer). As a result, inhibition of apoptosis by constitutive activation of survival signals is believed to be partially responsible for the mechanism of tumorigenesis (PIK3CA is implicated as an oncogene in ovarian cancer. Nature Genet. 21, 99-102, (1999); High frequency of mutations of the PIK3CA gene in human cancers. Science, 304, 554, (2004); Increased levels of phosphoinositol 3-Kinase activity in colorectal tumors. Cancer, 83, 41-47 (1998)).
In addition, the deletion or mutation of PTEN, a phospholipid phosphatase which hydrolizes PI(3,4,5)P3 that is one of the products of PI3K, has been reported in numerous cancers. Since PTEN functions as a suppressor of PI3K as a result of using PI(3,4,5)P3 as a substrate, deletion or mutation of PTEN is thought to lead to activation of PI3K in the PI3K signal.
On the basis of these reasons, useful anticancer action is expected to be obtained by inhibiting the activity of p110α in particular in cancers with elevated PI3K activity.
In this manner, Wortmannin (Non-Patent Document 1) and LY294002 (Non-Patent Document 2) are known to be specific inhibitors of PI3K, that are expected to be useful in the fields of immune diseases, anti-inflammatory agents, anticancer agents and the like.

Although numerous compounds having PI3K inhibitory action have recently been reported, none have yet to be used in clinical studies as pharmaceuticals in the form of anticancer agents, and have been limited to experimental studies on anticancer action based on the PI3K inhibitory action thereof, thus creating the desire for the prompt development of anticancer agents and the like having PI3K inhibitory action that are able to be used clinically.
On the other hand, compounds composed of a simple structure having a dimethylamino group at position 4 are known as multisubstituted bicyclic pyrimidines, and particularly 2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine derivatives (see Non-Patent Document 3). Although these derivatives have been suggested to have effect on hypoxemia accompanying respiratory diseases, their anticancer action or PI3K inhibitory action has neither been disclosed nor suggested.
Separate from this, 2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine derivatives having a nitrogen atom-mediated substituent or linear hydrocarbon group at 4-position have been reported to be effective against hypoxemia accompanying respiratory diseases (see Patent Document 1). However, their anticancer action or PI3K inhibitory action has neither been disclosed nor suggested.
In contrast, a compound of the present invention to be described to follow in the form of 2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine derivatives or 2-morpholin-4-yl-5,6,7,8-tetrahydro-pyrrido[2,3-d]pyrimidine derivatives having an unsaturated cyclic group directly bonded to a carbon atom at 4-position as in general formula (I) has heretofore not been known, and the usefulness of these derivatives as anticancer agents and the like having PI3K inhibitory action is also not known.    Patent Document 1: WO9105784    Non-Patent Document 1: H. Yano et al., J. Biol. Chem., 268, 25846, 1993    Non-Patent Document 2: C. J. Vlahos et al., J. Biol. Chem., 269, 5241, 1994    Non-Patent Document 3: Tetrahedron Letter 46 (2005), 1177-1179